Inhalation device and method

ABSTRACT

The present disclosure provides a method and device for delivering a pharmaceutical to the airway of a human or animal patient. In one aspect, the device includes a dose drum formed into a cylinder and including a plurality of dose compartments for containing individual doses. In another aspect, the device may include a reservoir containing a pharmaceutical material in bulk form and a metering recess for metering the pharmaceutical. material to form a pharmaceutical dose. Another aspect provides an inhaler with a combined reservoir and dosing chamber configured to contain multiple doses of a pharmaceutical material.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation application of U.S. patentapplication Ser. No. 14/056,828, filed Oct. 17, 2013, which in turn is adivisional application of U.S. patent application Ser. No. 12/985,158,filed Jan. 5, 2011, now U.S. Pat. No. 8,991,390, which claims priorityfrom the U.S. Provisional Application Ser. No. 61/292,401, filed Jan. 5,2010; U.S. Provisional Application Ser. No. 61/292,403, filed Jan. 5,2010; and U.S. Provisional Application Ser. No. 61/292,404, filed Jan.5, 2010; the contents of which are incorporated herein in theirentirety, by reference.

FIELD OF THE INVENTION

The present disclosure relates generally to the field of inhalationdevices. The disclosure has particular utility in connection with thedelivery of powdered medications to a patient using a dry powderinhaler, and will be described in connection with such utility, althoughother utilities are contemplated.

BACKGROUND OF THE INVENTION

Certain diseases of the respiratory tract are known to respond totreatment by the direct application of therapeutic agents. As theseagents are most readily available in dry powdered form, theirapplication is most conveniently accomplished by inhaling the powderedmaterial through the nose or mouth. This powdered form results in thebetter utilization of the medicament in that the drug is depositedexactly at the site desired and where its action may be required; hence,very minute doses of the drug are often equally as efficacious as largerdoses administered by other means, with a consequent marked reduction inthe incidence of undesired side effects and medicament cost.Alternatively, the drug in this form may be used for treatment ofdiseases other than those of the respiratory system. When the drug isdeposited on the very large surface areas of the lungs, it may be veryrapidly absorbed into the blood stream; hence, this method ofapplication may take the place of administration by injection, tablet,or other conventional means.

It is the opinion of the pharmaceutical industry that thebioavailability of the drug is optimum when the drug particles deliveredto the respiratory tract are between 1 to 5 microns in size. When thedrug particles need to be in this size range the dry powder deliverysystem needs to address a number of issues:

(1) Small size particles may develop an electrostatic charge onthemselves during manufacturing and storage. This may cause theparticles to agglomerate or aggregate, resulting in clusters ofparticles which have an effective size greater than 5 microns. Theprobability of these large clusters making it to the deep lungs thendecreases. This in turn results in a lower percentage of the packageddrug being available to the patient for absorption.

(2) The amount of active drug that needs to be delivered to the patientmay be of the order of 10s of micrograms. For example, in the case ofalbuterol, a drug used in asthma, this is usually 25 to 50 micrograms.Current manufacturing equipment can effectively deliver aliquots ofdrugs in milligram dose range with acceptable accuracy. So the standardpractice is to mix the active drug with a filler or bulking agent suchas lactose. This additive also makes the drug “easy to flow”. Thisfiller is also called a carrier since the drug particles also stick tothese particles through electrostatic or chemical bonds. These carrierparticles are very much larger than the drug particles in size. Theability of the dry powder inhaler to separate drug from the carrier isan important performance parameter in the effectiveness of the design.

(3) Active drug particles with sizes greater than 5 microns will likelybe deposited either in the mouth or throat. This introduces anotherlevel of uncertainty since the bioavailability and absorption of thedrug in these locations is different from the lungs. Dry powder inhalersneed to minimize the drug deposited in these locations to reduce theuncertainty associated with the bioavailability of the drug.

Prior art dry powder inhalers (DPIs) usually have a means forintroducing the drug (active drug plus carrier) into a high velocity airstream. The high velocity air stream is used as the primary mechanismfor breaking up the cluster of micronized particles or separating thedrug particles from the carrier. Several inhalation devices useful fordispensing this powder form of medicament are known in the prior art.For example, in U.S. Pat. Nos. 3,507,277; 3,518,992; 3,635,219;3,795,244; and 3,807,400, inhalation devices are disclosed having meansfor piercing of a capsule containing a powdered medicament, which uponinhalation is drawn out of the pierced capsule and into the user'smouth. Several of these patents disclose propeller means, which uponinhalation aid in dispensing the powder out of the capsule, so that itis not necessary to rely solely on the inhaled air to suction powderfrom the capsule. For example, in U.S. Pat. No. 2,517,482, a device isdisclosed having a powder containing capsule placed in a lower chamberbefore inhalation, where it is pierced by manual depression of apiercing pin by the user. After piercing, inhalation is begun and thecapsule is drawn into an upper chamber of the device where it movesabout in all directions to cause a dispensing of powder through thepierced holes and into the inhaled air stream. U.S. Pat. No. 3,831,606discloses an inhalation device having multiple piercing pins, propellermeans, and a self-contained power source for operating the propellermeans via external manual manipulation, so that upon inhalation thepropeller means aids in dispensing the powder into the stream of inhaledair. See also U.S. Pat. Nos. 3,948,264 and 5,458,135.

In prior U.S. Pat. Nos. 7,318,434, 7,334,577 and 7,779,837 incorporatedherein by reference, and assigned to the common assignee MicroDoseTechnologies, Inc., there is provided an improvement over prior artinhalers that utilize vibration to facilitate suspension of power intoan inhaled gas stream and which utilizes synthetic jetting to aerosolizedrug powder from a blister pack or the like. As taught in the aforesaidU.S. Pat. Nos. 7,318,434, 7,334,577 and 7,779,837 there is provided adry powder inhaler having a first chamber such as a blister pack orother container, for and holding a dry powder, and a second chamberconnected to the first chamber via a passageway for receiving anaerosolized form of the dry powder from the first chamber and fordelivering the aerosolized dry powder to a user. A vibrator is coupledto the dry powder in the first chamber. The vibrator is energized andcoupled to the first chamber and drives the powder from the chamber bysynthetic jetting.

As described in U.S. Pat. No. 7,080,644 also incorporated herein byreference, and also assigned to common assignee MicroDose Technologies,Inc., controlled aliquots or doses of a medication or drug arepre-packaged in a blister pack, which includes a frangible crowned topelement which may be conical, conical with a rounded point, rounded, orother raised shape configuration, and a bottom element which may be aflat web or membrane, or which itself may be of shaped configuration,e.g. conical, round, dish shaped, etc. for closely engaging with anunderlying vibrating element, the shape and size of which is chosen toprovide optimum controlled delivery of a given medication or drug. Thetop element of the blister pack is pierced with a piercing device suchas a sharp needle to form one or more apertures for delivery of themedication or drug contained within the blister pack. The hole patternand hole size is selected to provide optimization of delivery of theparticular medication or drug packaged therein.

SUMMARY OF THE INVENTION

The present disclosure in one aspect provides an improvement over theprior art devices such as discussed above by providing a compact sizepharmaceutical delivery package for delivering a pharmaceutical to theairway of a human or animal patient, containing a plurality ofindividual doses of a pharmaceutical. The delivery package is comprisedof a dose drum in the form of a cylinder which includes a plurality ofdose compartments for containing the individual doses of apharmaceutical and a sheath for surrounding the dose drum so as tocontain and segregate the plurality of individual doses of apharmaceutical in the dose compartments. The pharmaceutical deliverypackage may be formed to fit tightly around an outer surface of the dosedrum, wherein the sheath has at least two holes, including a first holefor filling the dose compartment with a pharmaceutical and a second holefor allowing the delivery of one of said plurality of individual dosesof a pharmaceutical. Alternatively the sheath may be formed of a tape orfoil that may be peeled away or perforated to access the pharmaceuticaldose contained therein.

Another aspect of the present invention provides an inhaler fordelivering a pharmaceutical to the airway of a human or animal patient.The inhaler comprises a dose drum formed into a cylinder, the dose drumincluding a plurality of dose compartments for containing individualdoses of a pharmaceutical; a sheath surrounding the dose drum; a dosechamber; and a flow channel, through which the individual dose isdelivering to the airway of the patient. The dose chamber may be aresonance chamber coupled to a vibration device, such as apiezo-electric device. The inhaler may further include a drive foradvancing the dose drum so that individual doses may be loaded into thedose chamber.

Another aspect of the present disclosure provides a method of deliveringa pharmaceutical material to the airway of a human or animal patient,the method comprising the steps of providing the pharmaceutical materialin a reservoir connected to a metering device; metering thepharmaceutical material with the metering device to form a singlepharmaceutical dose; moving the single pharmaceutical dose into a dosechamber; deaggregating the pharmaceutical material of the singlepharmaceutical dose; and delivering the single pharmaceutical dose fromthe dose chamber to the airway of the patient via a flow channel.

Another aspect of the present disclosure provides an inhaler fordelivering a pharmaceutical dose to the airway of a human or animalpatient. The inhaler includes a reservoir that contains a pharmaceuticalmaterial in bulk form, a metering recess for metering the pharmaceuticalmaterial to form a pharmaceutical dose; a dose chamber; and a flowchannel connected to the dose chamber, through which the pharmaceuticaldose is delivered from the dose chamber to the airway of the patient.The metering recess may be located on the outer surface of a meteringdrum, which is rotated to load the metering recess and load thepharmaceutical dose into the dose chamber, the metering drum beingsurrounded by a sheath. Alternatively, the metering recess may beenclosed between a first metering door and a second metering door. Thereservoir may be in the shape of a cylinder, the reservoir having acompression spring and piston for loading the pharmaceutical into therecess.

Another aspect of the present disclosure provides an inhaler fordelivering a pharmaceutical material to the airway of a human or animalpatient, the inhaler including a dose chamber with a chamber seal and aflow channel. The dose chamber is sized to contain multiple doses of thepharmaceutical material. The dose chamber may be a resonance chamberthat is coupled to a vibration device. The chamber seal may be connectedto a pressurized source, such as a nitrogen chamber or a vacuum. Thechamber seal may alternatively be connected to a desiccant source.

Yet another aspect of the present disclosure provides a method ofdelivering a single dose of a pharmaceutical material to the airway of ahuman or animal patient. Multiple doses of the pharmaceutical materialare contained in a resonance chamber. The pharmaceutical material isdeaggregated using a vibration device coupled to the resonance chamber,thereby causing a synthetic jet to expel some of the pharmaceuticalmaterial. The delivery of the pharmaceutical material is metered bycontrolling the duration of operation of the vibration device, and mayalso be controlled by optimizing the vibrating frequency of thevibration device.

Still another aspect of the present disclosure provides a pharmaceuticaldelivery package in the form of a cartridge, which may be reusable. Thecartridge contains a blister strip, formed on a substrate material, witha series of depressions or wells formed therein to contain individualdoses of a pharmaceutical. A foil is placed over the substrate to sealthe individual depressions, which serve to form individual blisters. Thecartridge also includes an aerosol chamber for deaggregating theindividual dose of a pharmaceutical and a device for advancing theblister strip relative to the aerosol chamber. The device for advancingthe blister strip may comprise one or more of an arm, a spring, a cam, agear, or a wheel. A blister detection switch facilitates controlling theadvancement of the blister strip to consistently position individualblisters relative to the aerosol chamber. The cartridge also includes adevice for removing the foil from the blister strip as it is advancedrelative to the aerosol chamber. The cartridge also includes amouthpiece and a flow channel, the flow channel connecting the aerosolchamber and the mouthpiece.

Another aspect of the present disclosure provides an inhaler fordelivering a pharmaceutical to the airway of a human or animal patient,utilizing the cartridge described above. The inhaler comprises a housingfor a vibrating device and a motor. The cartridge should be formed in aloop, with the blister strip being contained within the loop. Thehousing include an air inlet and a pressure sensor, the air inletinterfacing or mating with the flow channel of the cartridge. An o-ringor the like may be used to seal the connection between the air inlet andthe flow channel. The vibrating device, which may be a piezoelectricdevice, interfaces with the aerosol chamber of the cartridge. Theaerosol chamber may form a resonant chamber. The motor also interfaceswith the cartridge, providing the power for driving the device foradvancing the blister strip and the device for removing the foil.

Yet another aspect of the present disclosure provides an inhaler forautomatically delivering a pharmaceutical to the airway of a human oranimal patient. The inhaler comprises a housing containing at least onedose of a pharmaceutical, a pressure sensor, a vibrating device, and anaerosol chamber. The housing is connected to an interface for deliveringthe pharmaceutical to the patient, and through which the patientbreathes.

BRIEF DESCRIPTION OF THE DRAWINGS

Further features and advantages of the present disclosure will be seenfrom the following detailed description, taken in conjunction with theaccompanying drawings, wherein

FIGS. 1A-D, are drawings showing a pharmaceutical delivery package andinhaler of the present disclosure;

FIG. 2 is a drawing of a dose drum according to one example of thepresent disclosure; and

FIGS. 3A-C are drawings of a pharmaceutical delivery package and inhalerin an alternative example of the present disclosure;

FIG. 4 is a drawing of a pharmaceutical delivery package and deliverydevice according to another example of the present disclosure;

FIG. 5 is a drawing of a blister strip in accordance with the exampleshown in FIG. 4;

FIGS. 6A, 6B and 6C, are sectional views of the pharmaceutical deliverypackage shown in FIG. 4;

FIGS. 7A, 7B, 7C and 7D; 8A, 8B and 8C; 9A and 9B; and 10A, 10B and 10Care sectional views of the pharmaceutical delivery package and device ofFIG. 4 assembled together;

FIGS. 11A and 11B are drawings showing different views of an inhalationdevice in accordance with the present disclosure;

FIGS. 12A and 12B are drawings showing different views of anotherinhalation device in accordance with the present disclosure;

FIGS. 13A and 13B are drawings of a pharmaceutical material deliverypackage and inhaler in accordance with another example of the presentdisclosure.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

In the following description, reference is made to the accompanyingdrawings, which form a part hereof, and in which is shown, by way ofillustration, various embodiments of the present disclosure. It isunderstood that other embodiments may be utilized and changes may bemade without departing from the scope of the present disclosure.

The present disclosure provides an improved inhalation device and methodfor delivering a pharmaceutical to the airway of a patient. The intendedpatient may be either human or animal and the inhalation device shouldbe designed accordingly. The inhaler will be discussed in connectionwith a dry powder inhaler, but it is foreseeable that the presentdisclosure also will be useful in other types of inhalers.

In a first aspect, the present disclosure provides a package fordelivering discrete doses of a pharmaceutical, wherein the individualdoses are segregated into individual compartments arranged in a patternon a cylindrical dose drum. The individual doses may be deposited inindividual blisters, such as described in commonly-owned U.S.application Ser. No. 11/425,097, incorporated by reference herein. Theindividual doses may also be encapsulated in between membranes orbetween a membrane and a substrate, which may or may not be formed withpreformed dimples or other indentations to form part of thecompartments.

The individual compartments are arranged in a pattern on the cylindricaldose drum, which comprises a substrate formed into a cylindrical shape,the dose drum having an inner face and an outer face. The compartmentsthat contain individual doses of pharmaceuticals may be formed either onthe inner face of the substrate or the outer face of the substrate.Alternatively, the compartments may be formed protruding from thesubstrate at least partially on both the inner surface and outersurface. The substrate may be made from any suitable material, such asfor example a plastic, ceramic, paper or metal material, and may rangefrom transparent to opaque in appearance.

In one example of the present aspect of the disclosure, the dose drum isformed of a substrate material configured into a cylinder having anarrangement of dimples, each dimple comprising a recessed volumeconfigured to protrude from the substrate towards the center of the dosedrum. The individual dose compartments are formed by the dimples andconstrained by a sheath. Referring to FIGS. 1A-D, the sheath 20 may beformed to fit over the dose drum 10 according to a tight tolerance tosufficiently segregate the individual dose compartments 12. In thisregard, the sheath may comprise a tightly fitting sleeve that willsurround the dose drum for the purposes of containing each dose in itsrespective dose compartment and provide a moisture barrier for drugpreservation or stability. The drum sheath may be configured with afilling access porthole 21 in its surface to allow filling thecompartments with the chosen pharmaceutical, and a dose porthole 22 foremptying the dose compartment into dose chamber 30.

The sheath also may be formed of a membrane, such as a tape, foil, orfilm material, which may adhere to the dose drum in order to segregatethe individual doses. The membrane should be sufficiently strong to holdthe pharmaceutical material, but may also be designed to be perforatedor removed, with respect to a single dose compartment, as an individualdose is ready to be loaded into the dose chamber of an inhaler. Anexample of this alternative design is shown in FIG. 2, wherein thedimples (not visible) are formed in a helical pattern on the dose drumand the sheath comprises a strip of peelable film, foil or tape 15.

FIGS. 3A-C demonstrate another example of the present disclosure. Inthis example, the cylinder forming the dose drum is increased indiameter and reduced in height, forming a dose ring 60. The dose ringtakes the form of a circular band with compartments arrangedcircumferentially that will accept pre-metered drug weights and/orvolumes. The dose ring may be connected to a drive that will cause thering to advance in a rotary direction. Whereas the dose drum of FIGS.1A-D has a height that is greater than one row of dose compartments, thedose ring is only the height of a single row of dose compartments.

The sheath of the present disclosure is adapted in the present exampleto form ring sheath 70, a tightly fitting sleeve that surrounds the dosering for the purposes of containing each dose in its respective dosecontainer and providing a moisture barrier for preservation of thepharmaceutical substance. Similar to the sheath above, the ring sheathwill have a filling access porthole 71 and a dose porthole 72, thelatter of which is connected to the dose chamber. Similar to the dosedrum above, the ring sheath could be replaced with a peelable film, foilor tape that would be removed from each dose container just prior tobeing exposed to the dosing chamber.

The dose drum of the present disclosure may be loaded with individualdoses by being mated with a hopper containing a desired pharmaceutical,wherein the geometry of the individual dose compartments may serve tohelp meter the pharmaceutical.

The dose drum may be manufactured as a reusable component of an inhaleror as a disposable pharmaceutical dose container. The particular designmay instruct as to what materials are suitable for use in theconstruction of the dose drum.

Another aspect of the present disclosure provides an inhaler fordelivering a pharmaceutical to the airway of a human or animal patientutilizing a dose drum as described above. Referring again to FIGS. 1A-D,the inhaler comprises a dose drum 10, having a cylindrical substratewith a plurality of dose compartments 12 disposed thereon, a dosechamber 30 for accepting the individual pharmaceutical dose fromindividual dose compartments prior to delivery to the patient, and aflow channel 40 adjacent to the dose chamber for carrying thepharmaceutical to the airway of the patient.

The dose chamber 30 may comprise a resonance chamber, having a volumeand shape that will acoustically resonate at a chosen frequency. Theresonance chamber may in turn be coupled to a vibration device 50, suchas a piezoelectric transducer, to provide vibratory energy for utilizingthe acoustic properties of the resonance chamber to create a syntheticjet, as described in commonly-owned U.S. Pat. Nos. 7,318,434, 7,334,577and 7,779,837, the contents of which patents are incorporated herein byreference. The resonance chamber will receive an individual dose fromthe dose drum via dose porthole 22. Other examples of appropriatevibrating devices are disclosed in commonly-owned U.S. patentapplication Ser. No. 11/060,267, incorporated herein by reference.

The pharmaceutical material is then de-agglomerated and expelled intothe flow channel 40 by synthetic jetting through dosing holes 32. Thedosing holes promote the formation of a synthetic jet and facilitate thetransfer of the pharmaceutical from the dosing chamber into the flowchannel. The size of the holes can effect synthetic jet velocity and,ultimately, fine particle distribution.

The vibration device 50 is connected to a power supply 52. The vibrationdevice may further be connected to a frequency generator for optimalperformance, such as is described in commonly-owned co-pending U.S.application Ser. No. 12/392,686, incorporated herein by reference.

The inhaler may utilize a placement device for advancing the dose drumand aligning a particular dose compartment with the dose porthole of thesheath. The placement device may be, for example, a screw-drive device.The placement device may influence the chosen geometric arrangement ofthe dose compartments about the surface of the dose drum, such as shownin FIG. 2, for example.

The inhaler of the present disclosure may further comprise a chamberseal. The chamber seal may be in the form of a stopper that prevents thepassage of air into the dose chamber when the device is idle. This isincluded to further avoid unwanted exposure of individual doses tomoisture, oxygen and other contaminants. The chamber seal will open onauthorization signal from the inhaler, such when the inhaler senses thepatient inhaling (see, for example, U.S. Pat. No. 6,152,130 and U.S.Published Application Serial No. 2005/0183725, both assigned to thecommon assignee), and close after the dose is complete.

The chamber seal may further be connected to a pressurized nitrogenchamber by a nitrogen line that would fill the dose chamber withnitrogen between doses. It could also be connected to a vacuum source toevacuate air and moisture between doses. This may be done using at leasta portion of the same nitrogen line. The chamber seal may also beconnected to a desiccant chamber to absorb moisture transferred from theatmosphere during dosing.

The device of the present disclosure is susceptible to modification. Forexample, the dose chamber may be connected to multiple dose drums fordelivering combination pharmaceutical products.

Referring to FIGS. 4-11, another aspect of the present disclosureprovides an inhaler 101 utilizing a pharmaceutical delivery package inthe form of a cartridge 120, which cartridge may be reusable ordisposable. The principle of operation for this device is in similar tothe above-described device, and as further described in theafore-mentioned commonly-owned patents. In particular, U.S. PatentPublication No. 2010/0294278, incorporated by reference herein,describes a compact inhaler wherein the plurality of individual doses ofa pharmaceutical are contained in a rotary cassette. The cassettecontains a radial arrangement of individual blisters. The inhalerdescribed therein is similar in many ways to the present aspect of thedisclosure, except in that the rotary cassette is replaced by acartridge 120 containing a blister strip 130. Other differences may beapparent from the discussion that follows.

As seen in FIGS. 4-10, the inhaler generally comprises a housing 110 anda cartridge 120. As with previous disclosures, the inhaler includes amouthpiece 125 and a vibrating device 111. The mouthpiece is connectedto a flow channel 123, which is connected to an aerosol chamber 121,situated adjacent to the vibrating device. Unlike previous examples,however, the mouthpiece, flow channel and aerosol chamber areincorporated into the cartridge 120. This arrangement affords advantagesin reducing the size of the inhaler, drug protection and maintainingperformance.

The cartridge 120 contains a blister strip 130, which is comprised of asubstrate 133, such as a cold-formed plastic, with a series ofdepressions 132 or wells formed therein to contain the individual doses105. A foil, film or tape 135 is placed over the substrate to seal theindividual depressions, which form individual blisters 131 filled withthe pharmaceutical. The cartridge also includes an aerosol chamber 121,in which the individual doses are deaggregated according the methodsdescribed above and in the above-referenced applications. The aerosolchamber is preferably a resonance chamber, as described herein, and isbounded by a membrane 122 which contacts the vibrating device 111 whenassembled.

In the example shown, the cartridge also includes an advancing device140 for advancing the blister strip 130 relative to the aerosol chamber121. The device for advancing the blister strip may comprise an arm, aspring, a cam, a gear, a wheel, or any combination thereof. For example,FIG. 5 shows a pilot loop 148, which engages the blister strip, similarto a combination of a spring and an arm, in order to advance the blisterstrip. A blister detection switch 142 senses the advancement of theblister strip and facilitates controlling the advancement of the blisterstrip to consistently position individual blisters relative to theaerosol chamber 121.

The cartridge also includes a foil, film or tape removal device 141 forremoving the foil, film or tape from the blister strip as it is advancedrelative to the aerosol chamber. The foil, film or tape removal deviceincludes a take-up spool 145. Once the foil, film or tape is removed,the individual dose 105 is emptied into the aerosol chamber 121 fordelivery to the patient.

The arrangement of the blisters 131 on blister strip 130 facilitates, ornecessitates, the formation of the cartridge 120 in a loop, i.e., havingan open area 150 in the center. The housing includes a complementaryprotrusion 151. Within the protrusion, the housing contains a battery112 and motor 113. The motor turns gears 143,144, and thereby drives thetake-up spool 145 and foil removal device 141. The battery also providespower to the vibrating device 111, which may be a piezoelectric device.The battery also may be carried on the cartridge, and replaceable withthe cartridge. Alternatively, the blister strip may be advanced by athumb-screw, lever or clock mechanism, for example.

In the example shown, the housing further includes an air inlet 116,which connects to the flow channel 123 of the cartridge. An o-ring 119may be placed to facilitate a seal at the interface between the flowchannel and the air inlet. A pressure sensor 117, powered by thebattery, is located in a pressure sensor port 118 near the air inlet inorder to sense the breathing of the patient through the inhaler.

The present aspect is subject to modification in accordance with theother examples contained herein and in the commonly-owned patentsincorporated by reference. For example, the inhaler could be constructedwith the mouthpiece 125, flow channel 123, aerosol chamber 121, or anycombination thereof, forming part of the main housing 110 instead of thecartridge 120.

The present disclosure further provides a method and device for meteringa pharmaceutical material into a dosage amount and delivering that doseto the airway of a patient.

For example, one aspect of the present disclosure provides an inhalerfor delivering a pharmaceutical dose to the airway of a patient. Theintended patient may be either human or animal and the inhalation deviceshould be designed accordingly. The inhaler will be discussed inconnection with a dry powder inhaler, but it is foreseeable that thepresent disclosure will also be useful in modifying the designs of othertypes of inhalers.

The inhaler includes a reservoir, which contains a pharmaceuticalmaterial in bulk form. Referring to FIGS. 11A-B and FIGS. 12A-B, oneadvantageous shape of the reservoir may be a cylinder wherein thereservoir includes a piston 211 and compression spring 212 to assist inemptying the reservoir. Other shapes, such as spheres, cones and soforth, are also available and the figures are not meant to limit thepresent disclosure to the use of a cylindrical reservoir. Other forms ofback pressure may be used as an alternative to the piston andcompression spring. Similarly, many types of springs, aside from thehelical spring shown, are suitable for use with the inhalation device ofthe present disclosure. A significant advantage of the presentdisclosure is that the reservoir may be reloaded with bulk material andthe device may be reused.

The inhalation device of the present example also includes a meteringdevice for measuring the bulk pharmaceutical material into a singlepharmaceutical dose. The metering device should have a metering recessfor receiving the pharmaceutical material from the reservoir, themetering recess being sized to receive the desired dose.

Referring to FIGS. 11A and 11B, the metering device may be comprised ofa metering drum 220 and a sheath 230. In this example, the meteringrecess is formed as a metering dimple 222 on the outer surface of themetering drum. The dimple may be formed integral to the metering drumand should be manufactured to a precision volume for the purpose ofmetering the pharmaceutical dose.

The sheath 230 is formed to fit tightly around the outer surface of themetering drum, but not so tight as to prevent the metering drum fromrotating on its axis. The inhalation device may include a drive forrotating the metering drum. The rotation of the metering drum will alignthe metering recess 222 with one of at least two holes 231,232 in thesheath. The filling access porthole 231 is located on the sheath 230 atthe interface with the reservoir 210 and allows the metering recess 222to be filled with the pharmaceutical material 201. The dose porthole232, allows the metered pharmaceutical dose to be delivered to a dosechamber 240.

The dose chamber is configured to accept a single pharmaceutical dose,deaggregate the pharmaceutical material, and deliver the material to theflow channel 250. The dose chamber will be configured based upon thevarious methods that may be used for delivering medication to thepatient.

As with the previous examples, the dose chamber may comprise a resonancechamber, having a volume and shape that will acoustically resonate at achosen frequency. The advantages of this feature are discussed above.Further, as described above, the resonance chamber may be coupled to avibration device 244, such as a piezoelectric transducer, to providevibratory energy for utilizing the acoustic properties of the resonancechamber. The vibration device is connected to a power supply 246.

Referring to FIGS. 12A and 12B, the metering device of the presentdisclosure may comprise a metering recess or metering compartment thatis enclosed by at least two metering doors 225, 226. The first meteringdoor 225 sits between the metering compartment and the dose chamber 240.The second metering door 226 is between the metering compartment and thereservoir 210. Thus, when the second metering door opens (the firstmetering door remaining closed), the metering compartment may be loadedwith the pharmaceutical material 201. Then, when the first metering dooris opened (the second metering door remaining closed), the metered doseof pharmaceutical material may be placed in the dose chamber.

The present disclosure also provides a method for delivering apharmaceutical material to the airway of a patient, which may be humanor animal, by providing the pharmaceutical material in a reservoirconnected to a metering device; metering the pharmaceutical materialwith the metering device to form a single pharmaceutical dose; movingthe single pharmaceutical dose into a dose chamber; deaggregating thepharmaceutical material in the single pharmaceutical dose; anddelivering the single pharmaceutical dose from the dose chamber to theairway of the patient via a flow channel.

The method of the present disclosure may be used with a metering devicesuch as described herein comprising a metering drum and a sheath.Alternatively, the metering device may comprise a metering compartmentenclosed between a first metering door and a second metering door,wherein the second metering door is opened during the step of meteringthe pharmaceutical material, and the first metering door is openedduring the step of moving the single pharmaceutical dose into the dosechamber.

The dose chamber may serve as a resonance chamber, being coupled to avibration device, wherein the step of deaggregating the pharmaceuticalmaterial involves activating the vibration device to create a syntheticjet thereby delivering the single pharmaceutical dose from the dosechamber to the airway of the patient via a flow channel.

Another aspect of the present disclosure provides a device for meteringa pharmaceutical material into a selected dosage amount and deliveringthat dose to the airway of a patient. The device of the presentdisclosure is an inhaler that includes a chamber, which contains thepharmaceutical material, and a flow channel for delivering thepharmaceutical material to the patient. Basic functions of each of theseelements are described in the commonly-owned disclosures mentionedabove.

According to the present disclosure, multiple doses of a pharmaceuticalmaterial are stored within a combined reservoir and dosing chamber,which chamber is designed to store multiple doses of the pharmaceuticalmaterial, and meter out the pharmaceutical material in predetermineddoses.

Referring to FIGS. 13A and 13B, an inhaler is illustrated comprising acombined reservoir and dosing chamber which is configured to accept asupply of a pharmaceutical material, deaggregate the pharmaceuticalmaterial, and deliver the material to the flow channel 340. Thecombination reservoir and dosing chamber 330 comprises a resonancechamber, having a volume and shape that will acoustically resonate at achosen frequency. The resonance chamber and the advantages thereof arediscussed in detail above.

The inhaler of the present disclosure optionally may comprise a chamberseal 336. The chamber seal may be in the form of a stopper that preventsthe passage of air into the combined reservoir and dosing chamber whenthe device is idle. This is included to further avoid unwanted exposureof the pharmaceutical material to moisture, oxygen and othercontaminants. The chamber seal will open on authorization signal fromthe inhaler, such as when the inhaler senses the patient inhaling (seepreviously referenced commonly-owned patents and applications), andclose after the dose has been delivered.

The chamber seal 336 optionally may further be connected to apressurized nitrogen chamber by a nitrogen line 360 that would fill thecombined reservoir and dose chamber with nitrogen between doses. Chamberseal 336 also could be connected to a vacuum source to evacuate air andmoisture between doses. This may be done using at least a portion of thesame nitrogen line 360. The chamber seal also may be connected to adesiccant chamber to absorb moisture transferred from the atmosphereduring dosing.

The present disclosure allows the combined reservoir and dosing chamberto hold multiple doses to be expelled by synthetic jetting throughdosing hole 332, as described above. The dose size will be controlledelectronically by controlling the frequency and duration of eachactivation. Because the acoustic resonance will be affected by theremaining drug load, each dose activation preferably is electronicallytailored to provide consistent drug expulsion for every dose, e.g. bysensing movement of the vibration device and power source, and feedbackcontrolling the power delivered to the vibration device following theteachings of commonly-owned U.S. patent application Ser. No. 12/246,208,incorporated herein by reference.

An example of the present disclosure was tested using a blister that wasset up to serve as a resonance chamber for expelling multiple doses. A 4mg blister was loaded into the test device and the parameters were setto allow from approximately 1 mg of pharmaceutical to be expelled witheach dose. This was repeated for additional doses. Blisters were removedand weighed between actuations. In tables 1 and 2, below, it is shownthat by varying the “on-time”, or the duration of activating thevibration device, doses can be delivered with adequate predictability,even without optimization of the vibrating frequency and pattern.

TABLE 1 150 ms on-time 1^(st) dose 2^(nd) dose 1 1.058 1.262 2 1.2391.259 3 1.229 1.369 Mean 1.18 1.30 SD 0.10 0.03 % RSD 8.66 4.83 Max-Min0.18 0.11

TABLE 2 125 ms on-time 1^(st) dose 2^(nd) dose 3^(rd) dose 1 0.991 1.0540.932 2 1.09 1.052 0.808 3 0.931 1.108 0.914 Mean 1.00 1.07 0.88 SD 0.080.03 0.07 % RSD 8.00 2.97 7.57 Max-Min 0.16 0.06 0.12

The device of the present disclosure is susceptible to modification. Twoor more combined reservoir and dosing chambers may be incorporated in asingle inhaler for delivering combination pharmaceutical products.

Another aspect of the present disclosure provides a method fordelivering a pharmaceutical material to the airway of a patient, whichmay be human or animal. The method provides a pharmaceutical materialcontained in a combined reservoir and dosing chamber which also servesas a resonance chamber. The pharmaceutical material is then vibrationdeaggregated within the combined reservoir and dosing chamber, allowinga single dose to be delivered to the patient via synthetic jetting. Thestep of deaggregating the pharmaceutical material, thereby creating thesynthetic jet, may be performed by controlling the duration in whichpower is supplied to a vibration device 344 by a power source 352, asdescribed above. The power source also may be a source of frequencycontrol, for further controlling the effectiveness of the syntheticjetting.

The combined reservoir and dosing chamber also serves as a resonancechamber, by being coupled to a vibration device, wherein the step ofdeaggregating the pharmaceutical material involves activating thevibration device to create a synthetic jet thereby delivering thepharmaceutical from the combined reservoir and dosing chamber to theairway of the patient via a flow channel.

The present disclosure provides unique, space-saving designs which allowfor the creation of a smaller delivery devices, conserve materials,enable the pharmaceutical packaging to include an increased number ofmetered doses in a single package and provides for a mechanism to allowdelivery of a dry powder inhalation to patients not currently served bycommercial dry powder inhalers.

As used herein the term “pharmaceuticals” is intended to include allforms of drugs suitable for deliver by an inhaler. For example, whilethe present disclosure is particularly useful with dry powder inhalers(DPIs), the technology may be used to enhance other embodiments ofinhalers as well. Therefore, the pharmaceutical referred to in thepresent disclosure necessarily includes liquid forms of medications aswell as dry powdered medications.

Moreover, the term pharmaceuticals should not be strictly construed toexclude other useful substances such as phyto-pharmaceuticals, vitamins,hormones, steroids and other bioactive small molecules, peptides,proteins, etc.

It should be emphasized that the above-described embodiments of thepresent device, particularly, and “preferred” embodiments, are merelypossible examples of implementations and merely set forth for a clearunderstanding of the principles of the disclosure. Many differentembodiments of a pharmaceutical package for an inhaler described hereinmay be designed and/or fabricated without departing from the spirit andscope of the disclosure. All these and other such modifications andvariations are intended to be included herein within the scope of thisdisclosure and protected by the following claims. Therefore the scope ofthe disclosure is not intended to be limited except as indicated in theappended claims.

1-58. (canceled)
 59. An inhaler for delivering a pharmaceutical to the airway of a human or animal patient, comprising: a housing containing a vibrating device and a motor or mechanical advancing mechanism; a removable cartridge formed to interface with the housing, the cartridge forming a loop surrounding an opening formed completely through a center portion of the cartridge, wherein the removable cartridge further comprises: a strip arranged within the loop of the cartridge having a plurality of blisters containing individual doses of a pharmaceutical; a flow channel; an air inlet that interfaces with the flow channel; an aerosol chamber connected to the flow channel, wherein the aerosol chamber and the vibrating device form a resonance chamber for deaggregating the pharmaceutical; a mouthpiece connected to the flow channel for delivering the pharmaceutical to the patient; a device for advancing the strip relative to the aerosol chamber; and a device for opening an individual blister adjacent the aerosol chamber whereupon an individual dose of the pharmaceutical is delivered to the aerosol chamber; wherein the vibrating device interfaces with the aerosol chamber.
 60. The inhaler of claim 59, wherein the housing further includes a pressure sensor located in or near the air inlet.
 61. The inhaler of claim 59, wherein the device for advancing the strip is driven by the motor or at least one mechanical advancing mechanism contained within the housing.
 62. The inhaler of claim 59, wherein the vibrating device is a piezoelectric device.
 63. The inhaler of claim 59, wherein the pharmaceutical is in a powder form. 